The objective of this project is an integrated multidisciplinary approach to drug design. In particular, the concept of pharmacophore will be tested in a variety of systems by systematic examination of its consequences through the active analog approach. Exhaustive innumeration of possible orientations of candidate functional groups for the pharmacophore will be examined in series of active compounds. Once a pharmacophore consistent with the entire set of compounds is obtained, then it will be used to map receptor sites. Development of this approach is obtained, then it will be used to map receptor sites. Development of this approach conceptually as well as algorithmically is a primary objective. The computational complexity of exhaustive search requires development of parallel processing through multiarray processors as a prologue to VLSI implementation. Alternative formulations of the problem by distance geometry will also be explored. This approach will be applied to isolated enzyme systems which transform steroids, or hydrolyze peptides in the design of mechanism-based inhibitors. The receptor-bound conformation of peptide hormones, i.e. angiotensin, thyroliberin, morphiceptin and conformational constraints and their conformational analysis. Larger macromolecular systems such as enzymes of known structure and models of membrane pores will also be studied.